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Synthesis and evaluation of 90 Y‐DOTA‐Colchicine conjugate in murine fibrosarcoma model
Author(s) -
Satpati Drishty,
Korde Aruna,
Pandey Usha,
Dhami Prem,
Banerjee Sharmila,
Venkatesh Meera
Publication year - 2006
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.1115
Subject(s) - dota , colchicine , chemistry , biodistribution , conjugate , fibrosarcoma , pharmacokinetics , high performance liquid chromatography , pharmacology , stereochemistry , in vitro , chromatography , biochemistry , medicine , chelation , organic chemistry , pathology , mathematical analysis , mathematics
Colchicine is a cytotoxic bioactive alkaloid that exhibits its action by microtubular binding. With an aim to develop a tumor targeted radio‐therapeutic agent, colchicine has been functionalized to trimethylcolchicinic acid and conjugated to the isothiocyanato derivative of DOTA (1,4,7,10‐tetraaza cyclododecane tetracetic acid). DOTA coupled colchicine was radiolabeled with 90 Y, one of the most commonly used therapeutic radioisotope. Complexation of 200 µg of the conjugate with 90 Y was carried out at pH 4.5 with an incubation time of 45 min at 70°C. Complexation yield of 90 Y‐DOTA‐NCS‐colchicine was confirmed to be >98% using C‐18 reverse phase HPLC system. 90 Y‐colchicine complex could be differentiated from 90 Y‐ p ‐NCS‐benzyl‐DOTA on the basis of difference in their retention times 8 and 4 min, respectively in a standardized HPLC system. Biodistribution studies in Swiss mice fibrosarcoma tumor model showed an uptake of ∼0.8% ID/g tumor at 3 h.p.i. that was retained till 24 h.p.i. 90 Y‐DOTA‐NCS‐colchicine complex showed excellent pharmacokinetics with major portion of the radioactivity being excreted out within 3 h.p.i. and no accumulation of radioactivity in vital organs. Copyright © 2006 John Wiley & Sons, Ltd.